A. Herpes Simplex Virus Type 1 (HSV-1) Glycoprotein E
Glycoprotein E (gE) is one of ten documented herpes simplex virus type I (HSV-1) glycoproteins. In HSV-1 infected cells, gE is synthesized as an unglycosylated peptide having a molecular weight of 59 kDa. The unglycosylated polypeptide is cleaved and partially glycosylated to produce a precursor gE (pgE) of approximately 65 kDa, which is then further glycosylated to the mature form of gE with a molecular weight of about 80 kDa.
The ten HSV glycoproteins are located on the surface of the virus, some of which are reported to be the primary inducers and targets of both humoral (antibody) and cell-mediated immune responses to HSV-1 infection. In one study, Blacklaws et al. have shown glycoproteins B and D to induce high neutralizing antibody titers and to protect from latent herpes infection (1). They also found, however, that vaccinia expressed glycoproteins G, H and I produced no protective response in immunized mice (1), and that vaccinia expressed gE demonstrated only a very weak neutralizing antibody response against HSV. Blacklaws et al. also found that vaccination with gE expressed by vaccinia virus did not protect against the establishment of latent infections, nor did it protect mice against lethal HSV-1 challenge (1). In another study, Para et al. found that, only in the presence of complement, antibodies against immunoaffinity purified gE neutralized HSV-1 infectivity. But even then, the neutralization titers were low, and the extent of the anti-gE antibodies' role in neutralization was not determined (2).
In contrast to these reports, we have expressed in a baculovirus system, gE that is capable of eliciting a strong protective immune response against HSV-1 infection. In fact, vaccination with our recombinant baculovirus expressed gE induced high neutralizing antibody titers, a DTH response and protected against lethal HSV-1 challenge in mice. The neutralizing antibody titers we obtained were much higher than titers obtained by either Para et al. against their immunoaffinity purified gE, (2) or Blacklaws et al. against their vaccinia expressed gE (1). In addition, our neutralizing antibody titers against baculovirus expressed gE were only partially complement dependent, which in contrast to Para's results (2), required the presence of complement with their immunoaffinity purified gE for even low neutralizing activity. This ability to produce large quantities of high quality bioactive gE, is critical in the development of an effective vaccine against HSV.